C. perfringens is a ubiquitous gram positive, spore-forming, anaerobic organism, found in many environments surrounding poultry production, or other agricultural activities associated with animal rearing, including soil, dust, feces, feed, litter, rodents, and the intestinal contents of asymptomatic animals. The toxins produced by C. perfringens strains cause necrotic enteritis (NE) in severe cases and have the ability, at lower doses, to cause a subclinical necrotic enteritis with thickening of the intestinal mucosa and decreased length of microvili in the ileum. The collective impact of C. perfringens colonization is to reduce the absorptive surface in the intestinal tract with a consequent reduction in the ability of birds, and most likely other animals including humans, to benefit from nutrients in food, resulting in a reduced rate of growth. C. perfringens induces cellulitis and gangrenous dermatitis and is becoming an increasing concern in turkeys as well. Additionally, it is a frequent cause of gas gangrene in humans.
It is interesting to note that the majority of antibiotics added to poultry feed that are most effective as growth promoters are active against gram-positive bacteria, such as Clostridia. In addition, the most prevalently used ionophore anti-coccidial drugs also exhibit anti-clostridial activities. Therefore, C. perfringens infections and NE have been traditionally controlled by addition of Antimicrobial Growth Promoters (AGP) and coccidiostats, to control Eimeria infections, in the animal feed. Large quantities of antimicrobials were used as AGP and as prophylaxis against enteric bacterial pathogens, including C. perfringens. The use of AGP has been condemned due to concerns about increased antibiotic resistance in human pathogens. Consequently, the recent increase in sporadic outbreaks and widespread sub-clinical NE is linked to the withdrawal of AGP. This had been observed initially in Scandinavian countries following the ban on AGP in the early nineties. Furthermore, the decline in use of ionophore coccidiostats, which can prevent C. perfringens lesions, due to the introduction of vaccines to prevent Eimeria infections, has exacerbated the resurgence of NE. Thus, NE is a re-emerging disease and a major threat to the current objective of ‘antimicrobial-free’ poultry farming.
C. perfringens can cause a range of health problems in infected birds, ranging from a subclinical infection which can result in poor feed conversion caused by decreased digestion and adsorption, to necrotic enteritis, resulting in a variety of symptoms including severe depression, decreased appetite, reluctance to move, diarrhea and ruffled feathers, often leading to death. Clinical illness is usually short, with birds often simply found dead. Onset of disease symptoms generally occurs in broilers from two to five weeks of age, coinciding with the disappearance of maternal antibodies. However, NE has also been reported in layers of various ages. Gross lesions typically involve the ileum and jejunum, although cecal lesions can occur. Intestines are friable and distended with gas and fluid and a diphtheritic membrane is often found in the mucosa. Subclinical infection with C. perfringens can lead to economic losses, due to reduced growth rates and poor feed conversion. It is likely that losses due to subclinical infections may constitute a larger problem overall than losses due to acute disease. Occasionally, cholagniohepatitis can result, leading to condemnation losses at slaughter.
In a recent study, the Food Safety and Inspection Service (FSIS) determined Salmonella serotypes isolated from swine, ground turkey, ground beef and broilers in processing plants participating in the Hazard Analysis and Critical Control Point (HACCP) systems for pathogen reduction and found that 87% of the Salmonella isolates were from poultry sources. Using data from the Centers for Disease Control and Prevention collected in 2005, it is evident that some Salmonella serotypes that are most frequently isolated from humans are also very prevalent in poultry, with 8 of the Salmonella serotypes predominantly isolated from poultry being represented in the top 20 serotypes isolated from humans
Hence, there is a need in the art for an inexpensive, effective oral vaccine against C. perfringens for control of both subclinical infections and NE in poultry. However, vaccines that are effective in controlling such infections in poultry might have applications in control of C. perfringens infections in other animal species and even in humans. In addition, such vaccines if they reduced Salmonella infection and colonization in farm animals would benefit food safety by lessening the likelihood for transmission of Salmonella through the food chain to humans.